mitochondrial respiratory supercomplex decoded

[anciendaze]

To give everyone some perspective on the incomplete nature of the underlying science I wish to link this announcement of a study that has finally recognized how the different protein subunits in a normal mitochondrial respiratory supercomplex fit together. The complete, but less intelligible, paper is here.

Up until this time we were all in considerable darkness about what was going on in these vital organelles of every living cell. Even when we knew all the pieces, what we had was like a bag of lego pieces, not a structure. We still don't know a great deal about how this relates to function, although there are now some very interesting conjectures to consider.

The human mitochondrial genome itself has only 37 genes, and only 13 of these code for proteins. A mitochondrion contains about 3,000 different proteins, most of which are coded in nuclear DNA on chromosomes. If we are just now figuring out how the pieces literally vital for respiration fit together in healthy mitochondria, you can form your own estimate of how far we are from completely understanding mitochondrial diseases.

 

[Ingrid88]

Holy cow! this is complicated! All the 'mitochondrial support' we were trying out is a stab in the dark according to this. I do not claim to understand it - only that it is too complicated to base simple supplement strategies on it.
And for me, approaching 70 this will take too long to be unraveled.
Still, its interesting, thank you @anciendaze. I hope it will help our younger PWME in perhaps 10 years time?

 

[anciendaze]

@Ingrid88

You don't have to understand everything to treat an illness empirically. I'm still not certain we've learned everything about lithium salts and bipolar illness, but they have been working to reduce manic episodes in many people for many years when I definitely could say we did not understand how it worked.

I do think it is vitally important to distinguish different causes of "CFS", including energy deficits caused by mitochondrial diseases. Any approach which assumes there is no physiological illness to treat will lump together any number of conditions with different etiologies, making it virtually impossible to advance research and treatment.

Here on this forum I've already encountered people with known defects in energy metabolism, ion channels, and autoantibodies. All these were initially told they had the same condition, possibly a mental illness. Some do benefit from simple treatments, like supplements of magnesium, but this isn't "one size fits all". We've also turned up a patient who had flash pulmonary edema in response to an infusion of magnesium. This is life threatening.

From research by Systrom's group in Boston using iCPETs we know that some people who exhibit shortness of breath during exercise suffer from low cardiac fill pressure. Based on less invasive testing it is not at all apparent which patients in a group with a single such complaint may turn out to have this definite objective cardiovascular problem.

Testing to determine something about the nature of the energy problem in each particular patient needs to take place so we don't continue giving people who are desperate to get their lives back advice that is good for a different person, but may be harmful for them.

Based on other testing for patients with CPETs on consecutive days we know that some patients experience a prolonged loss of aerobic capacity after heavy exercise. It doesn't really matter how common this is if the patients you are treating may decline in performance to the point they cannot care for themselves. You are likely to kill them or drive them to suicide if you push them to exercise while their condition deteriorates. The pertinent question then becomes how many excess deaths do you consider acceptable for a treatment option that benefits others?

(I know people with diseases which show up in early adult years and make them only 1 in 100,000 live births. Most practicing doctors have never heard of this even though the reality of the condition is documented in medical literature. Doctors ignore this because there is a great deal of medical literature to read, and they are unlikely to see a single such patient in their career. Is killing a mere 3,000 Americans with such a single condition acceptable public health practice? How many different rare conditions are there? What would the final total of excess deaths be due to a policy decision that ignored rare conditions?)

Nobody wants to answer such a question, which is the central problem with a current state of the art that confounds medical problems as different as acquired mitochondrial defects, other metabolic defects, endothelial dysfunction, dysautonomia and ion channelopathies with functional psychosomatic conditions.

(Even if those functional conditions are the problem for a particular patient, current therapies have very poor record for long-term success. It is not at all uncommon to meet patients who have been treated repeatedly and discharged repeatedly as "recovered". Either those patients have some other condition, or current treatment options have dismal rates of relapse. This kind of therapy is not even a cheap alternative. There was even a book titled When Talk Is Not Cheap.)